Liu Hsuan-Liang, Lin Jin-Chung
Department of Chemical Engineering, Graduate Institute of Biotechnology, National Taipei University of Technology, No 1 Sec 3 Chung-Hsiao E Rd, Taipei, Taiwan 10608.
J Biomol Struct Dyn. 2004 Apr;21(5):639-50. doi: 10.1080/07391102.2004.10506954.
In this study, structural model of the pore loop region of the voltage-gated potassium channel Kv1.1 from human Homo sapiens was constructed based on the crystallographic structure of KcsA by structural homology. The pore loop region of Kv1.1 exhibits similar folds as that of KcsA. The structural feature of the selectivity filter of Kv1.1 is nearly identical to that of KcsA, whereas most of the structural variations occur in the turret as well as in the inner and outer helices. Molecular docking experiments of the scorpion toxin Tc1 from Tityus cambridgei to the outer vestibule of KcsA as well as Kv1.1 were subsequently performed with various initial Tc1 orientations. Tc1 was found to form the most stable complexes with these two K+ channels when the side chain of Lys14 occupies the pore of the selectivity filter through electrostatic interaction. Tc1 binds preferentially towards Kv1.1 than KcsA due to stronger hydrophobic and electrostatic interactions formed between the toxin and the selectivity filter and outer vestibule of Kv1.1. Furthermore, surface complementarity of the outer vestibules of the channels to the Tc1 spatial conformations also plays an important role in stabilizing both the Tc1/KcsA and Tc1/Kv1.1 complexes.
在本研究中，基于嗜盐栖热放线菌钾通道（KcsA）的晶体结构，通过结构同源性构建了人类电压门控钾通道Kv1.1孔环区域的结构模型。Kv1.1的孔环区域与KcsA呈现出相似的折叠结构。Kv1.1选择性过滤器的结构特征与KcsA几乎相同，而大多数结构变化发生在炮塔以及内螺旋和外螺旋中。随后，对来自剑桥肥尾蝎的蝎毒素Tc1以各种初始取向与KcsA以及Kv1.1的外前庭进行了分子对接实验。当赖氨酸14的侧链通过静电相互作用占据选择性过滤器的孔时，发现Tc1与这两种钾通道形成最稳定的复合物。由于毒素与Kv1.1的选择性过滤器和外前庭之间形成更强的疏水和静电相互作用，Tc1对Kv1.1的结合优先于KcsA。此外，通道外前庭与Tc1空间构象的表面互补性在稳定Tc1/KcsA和Tc1/Kv1.1复合物中也起着重要作用。
